Effects of Primary Mast Cell Disease on Hemostasis and Erythropoiesis

Mast cell disease is an epigenetically and genetically determined disease entity with very diverse clinical manifestations in potentially every system and tissue due to inap pro priate release of variable subsets of mast cell mediators together with accumulation of either morphologically normal or altered mast cells. Easy bruising, excessive bleeding, and aberrancies of erythropoiesis can frequently be observed in patients with mast cell disease. A thorough history, including a family history, will guide the appropriate work-up, and laboratory evaluations may provide clues to diagnosis. In recent years, our understanding of the involvement of coagulation and anticoagulant pathways, the fibrinolytic system, and erythropoiesis in the pathophysiology of mast cell disease has increased considerably. This review summarizes current knowledge of the impact of the disturbed hemostatic and erythropoietic balance in patients with mast cell disease and describes options of treatment.     

生体功能性医用材料止血功能的研究报告

对不同分子量、不同脱乙酰度、不同添加成分的甲壳素复合材料———五种生体功能性医用材料的止血功能进行了体外动态凝血和血小板粘附的探索试验和比较分析。     

Exposure of Mice to Thirdhand Smoke Modulates In Vitro and In Vivo Platelet Responses

Smoking is a risk factor for a variety of deleterious conditions, such as cancer, respiratory disease and cardiovascular disease. Thrombosis is an important and common aspect of several cardiovascular disease states, whose risk is known to be increased by both first- and secondhand smoke. More recently, the residual cigarette smoke that persists after someone has smoked (referred to as thirdhand smoke or THS) has been gaining more attention, since it has been shown that it also negatively affects health. Indeed, we have previously shown that 6-month exposure to THS increases the risk of thrombogenesis. However, neither the time-dependence of THS-induced thrombus formation, nor its sex dependence have been investigated. Thus, in the present study, we investigated these issues in the context of a shorter exposure to THS, specifically 3 months, in male and female mice. We show that the platelets from 3-month THS-exposed mice exhibited enhanced activation by agonists. Moreover, we also show that mice of both sexes exposed to THS have decreased tail bleeding as well as decreased thrombus occlusion time. In terms of the role of sex, intersex disparities in thrombus development and hemostasis as well as in platelet aggregation were, interestingly, observed. Together, our findings show that exposing mice to THS for 3 months is sufficient to predispose them to thrombosis; which seems to be driven, at least in part, by an increased activity in platelets, and that it does not manifest equally in both sexes.     

Diagnosing Czech Patients with Inherited Platelet Disorders

A single-center study was conducted on 120 patients with inherited disorders of primary hemostasis followed at our hematological center. These patients presented a variety of bleeding symptoms; however, they had no definitive diagnosis. Establishing a diagnosis has consequences for the investigation of probands in families and for treatment management; therefore, we aimed to improve the diagnosis rate in these patients by implementing advanced diagnostic methods. According to the accepted international guidelines at the time of study, we investigated platelet morphology, platelet function assay, light-transmission aggregometry, and flow cytometry. Using only these methods, we were unable to make a definitive diagnosis for most of our patients. However, next-generation sequencing (NGS), which was applied in 31 patients, allowed us to establish definitive diagnoses in six cases (variants in ANKRD26, ITGA2B, and F8) and helped us to identify suspected variants (NBEAL2, F2, BLOC1S6, AP3D1, GP1BB, ANO6, CD36, and ITGB3) and new suspected variants (GFI1B, FGA, GP1BA, and ITGA2B) in 11 patients. The role of NGS in patients with suspicious bleeding symptoms is growing and it changes the diagnostic algorithm. The greatest disadvantage of NGS, aside from the cost, is the occurrence of gene variants of uncertain significance.     

Physiological hemostasis based intelligent integrated cooperative controller for precise fault-tolerant control of redundant parallel manipulator

This paper focuses on precise fault-tolerant control for actual redundant parallel manipulator. Based on kinematic redundancy, some unnoticed influences such as mechanical clearance have been considered to design a more precise and intelligent fault-tolerant plan for actual plants. According to regulation principles in human hemostasis system, a bio-inspired intelligent integrated cooperative controller (BIICC) is developed including system structure, algorithm and step in parameter tuning. The proposed BIICC optimises partial error signal and improves control performance in each sub-channel. Moreover, the new controller transfers and disposes cooperative control signals among different sub-channels to achieve an intelligent integrated fault-tolerant system. The proposed BIICC is applied to an actual 2-DOF (degrees of freedom) redundant parallel manipulator where the feasibility of the new controller is demonstrated. The BIICC is beneficial to control precision and fault-tolerant capability of redundant plant. The improvements are more obvious in cases where extra actuators of redundant manipulator are broken.     

医用改性海藻纤维的制备及性能研究

选用海藻酸钠、仙鹤草为原料,添加一定量聚乙烯醇(PVA),配制共混纺丝液,采用湿法纺丝技术制备医用改性海藻纤维,并对其相关性能进行了测试。测试结果表明:添加了PVA和仙鹤草的海藻纤维与纯海藻纤维相比较,其干、湿态下的断裂强度和断裂伸长率均有所增加,纤维水浸液对水的pH值影响较小,纤维吸液能力增强,止血效果显著,抗菌性能符合国家标准。     

Molecular Mechanisms of RADA16-1 Peptide on Fast Stop Bleeding in Rat Models

Ionic self-assembly of the peptide RADARADARADARADA (RADA16-1) may form a well-defined nanofiber and eventually a hydrogel scaffold, with a water content of over 99.5%. This leads to the establishment of a nanofiber barrier that can be used to achieve complete hemostasis in less than 20 s in multiple tissues and in a variety of different wounds. In the present study, the nanofiber scaffolds of RADA16-1 peptide were sonicated into smaller fragments to identify possible molecular mechanisms underlying the rapid cessation of bleeding associated with these materials. Atomic force microscopy (AFM), circular dichroism (CD), and rheometry were also used to evaluate the re-assembly kinetics of this peptide. A bleeding control experiment was performed in animal models to uncover the molecular mechanisms underlying this fast hemostasis. In this way, these sonicated fragments not only quickly reassembled into nanofibers indistinguishable from the original material, but the degree of reassembly was also correlated with an increase in the rigidity of the scaffold and increased as the time required for hemostasis increased.     

Preparation of Chitosan-based Microspheres for Rapid Hemostasis

Rapid control of heavy hemorrhaging is critical to save the life of injured individuals.Herein,we developed a novel hemostat employing chitosan-based microspheres,which was prepared by sequential microemulsion of chitosan solution,sol-gel phase transition,and surface modification by 3,4-dihydroxyhydrocinnamic acid(HCA).HCA-modified chitosan microspheres(CSMS-HCA)displayed a porous structure,with a high specific surface area(~211.3 m²/g),accelerating their rapid absorption of blood and concentrating red cells and platelets.The CSMS-HCA exhibited much better in vitro and in vivo hemostatic efficacy than porous chitosan microspheres did.Such a rapid hemostat in the form of microspheres is highly effective in treating deep and irregular wounds,owing to easy accessibility to injured sites.     

Hemostatic multilayer coatings

Spray layer-by-layer assembly is used to create hemostatic films containing thrombin and tannic acid. The spray assembly technique enables coating of porous and absorbent commercial gelatin sponges with these films. Coated sponges are able to promote instantaneous hemostasis in a porcine spleen bleeding model.     

Differential effect of materials for surface hemostasis on red blood cell morphology

The design of devices for surface (topical) hemostasis has been based on maximizing activation of platelets and accelerating coagulation pathways. The studies reported herein examine another aspect of blood contact with topical hemostasis materials, i.e., surface binding of red blood cells (RBCs) and related alterations in RBC morphology. Whole blood was allowed to contact poly-N-acetyl glucosamine (pGlcNAc) containing materials: pGlcNAc nanofibers with parallel polymer alignment (beta-pGlcNAc), chitin, and chitosan. The effect on RBC morphology and function via contact with the artificial surfaces on the cell's morphology was examined with scanning and transmission electron microscopy (TEM). beta-pGlcNAc was found to densely bind RBCs and induce a stomatocytic-like morphology. Chitin and chitosan also bound RBCs, but with approximately 10-fold lower levels and with less distinct general morphologies. beta-pGlcNAc is thus unique in the nature of its interaction with RBCs. These studies indicate that the differential ability of various materials to bind and alter the morphology of RBCs at the artificial surface interface with blood is an important consideration in the design of devices for surface hemostasis.